Radiopharmaceutical purity for nuclear medicine
verified by thin layer chromatography
Mark Moskovitz, PhD
Gary Witman, MD
Radiopharmaceuticals are defined as
pharmaceuticals incorporating one or more
radioactive isotopes (i.e.radionuclides). The
radiochemical purity of a radiopharmaceutical
preparation represents that fraction of the
radionuclide present in its stated chemical form. It
is essential for technologists working in nuclear
medicine to know precise drug purity in order to
accurately determine the actual radiation dose being
administered to a patient.
Radiopharmaceuticals in the hospital setting may
be administered either orally or intravenously, and
are useful for both diagnostic and therapeutic
applications. Diagnostic studies include routinely
performed clinical procedures such as bone scans,
kidney scans, thyroid scans, PET scans, etc. In more
than 90% of instances the radioactive compounds are
utilized for diagnostic purposes. An example for the
therapeutic use of a radiopharmaceutical would
include the treatment of a hyperactive goiter of the
thyroid gland by administering radioactive iodine.
In this instance the radiation administered as
properly dosed provides the desired therapeutic
benefit.
A radiopharmaceutical contains at least two major
components:
-
a radionuclide that produces the desired
radiation characteristics
-
a chemical compound with structural or chemical
properties that determines the in vivo distribution
and physiological behavior of the
radiopharmaceutical
Impurities may alter the biodistribution of
radiopharmaceuticals, resulting in distorted
scintigraphic images. As a consequence there may be
either major diagnostic or therapeutic failures
using the radiopharmaceutical agent. Adequate
quality control should detect both radiochemical
purities as well as the stability of the bound
compound.
The purity of a radiopharmaceutical agent is
essential for estimating the administered radiation
dosage. Impurities may arise from radionuclide
production, subsequent chemical procedures,
incomplete preparative separation or chemical
changes during storage. Radiochemical impurities in
radiopharmaceuticals may result from decomposition
and from improper preparative procedures. Radiation
causes decomposition of water, a main ingredient of
most radiopharmaceuticals. This leads to the
production of reactive hydrogen atoms and hydroxyl
radicals, hydrated electrons, hydrogen, hydrogen
ions and hydrogen peroxide.
Radiopharmaceuticals are usually used in tracer
quantities, and as such there is none of the dose
response relationships associated with conventional
drug administration.
In the hospital setting the radiochemical purity
of radiopharmaceuticals is best determined by thin
layer chromatography. Of the many procedures used in
nuclear medicine for performing purity analysis
planar chromatography is the preferred procedure.
Radiopharmaceuticals have short half lives and speed
is an essential element for quality control. Besides
speed and convenience, the other major advantage of
planar chromatography over column and elution
methods is that the total amount of applied
radioactivity remains on the chromatoplate (TLC
plate). This enables quantification of various
segments using a suitable collimated counter under
standard conditions.
The common procedural characteristic for all
forms of planar chromatography requires that the
sample be applied to a stationary medium with an
appropriate mobile phase. What is becoming
commonplace is the use of instant TLC (ITLC), a
process which increases the migration speed of the
mobile phase.
Multiple studies published in the literature
demonstrate that TLC chromatography is now the
standard for the evaluation of radiopharmaceutical
purity. With SPECT and PET scanning complimenting
fast speed CT scan imaging in both the outpatient as
well as hospital setting, the role of diagnostic
radiopharmaceutical evaluation using TLC techniques
will continue to take on a much more significant
role in health care delivery.
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